PRETERM LABOR AND FETAL SEQUELAE: ROLE OF MYCOPLASMAS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。我们在非人灵长类动物中建立了第一个实验模型，其中通过羊膜内接种已知数量的生殖器生物解脲支原体或人支原体来建立感染。慢性插管妊娠恒河猴实验性羊膜内感染（IAI）后，促炎细胞因子(白细胞介素（IL)-1 β、肿瘤坏死因子(TNF) α、IL-6、IL-8）、前列腺素（PG）E2、pgf2 α和基质金属蛋白酶-9 （MMP-9）的序列上调。在所有病例中，随后是子宫收缩、阵痛和分娩。羊膜内细胞因子和（PG）浓度与生殖道支原体菌落计数平行上升。解脲脲菌对胎儿肺泡和终末气道的相关肺损伤比人支原体感染更严重。我们的工作假设是，产前使用适当的抗生素和特异性抗炎药治疗宫内解脲脲菌或人支原体感染可以抑制早产，延缓早产，改善或预防胎儿/新生儿肺部疾病。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We developed the first experimental model in nonhuman primates in which infection is established by the intraamniotic inoculation of known quantities of the genital organisms Ureaplasma urealyticum or Mycoplasma hominis. Following experimental intraamniotic infection (IAI) in chronically-catheterized, pregnant rhesus monkeys, there is a sequential upregulation of proinflammatory cytokines (interleukin (IL)-1beta, tumor necrosis factor (TNF)alpha, IL-6, IL-8), prostaglandin (PG)E2 and PGF2alpha, and matrix metalloproteinase-9 (MMP-9). This is followed in all cases by uterine contraction, labor and delivery. Intraamniotic cytokine and (PG) concentrations rise in parallel with counts for genital mycoplasma colonies. Associated fetal lung damage in alveoli and terminal airways is more severe with U. urealyticum than with M. hominis infection. It is our working hypothesis that prenatal treatment of intrauterine U. urealyticum or M. hominis infection with appropriate antibiotics and specific anti-inflammatory agents will inhibit preterm labor, delay premature delivery, and ameliorate or prevent fetal/neonatal lung disease.